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Article ; Online: Gasdermin D promotes influenza virus-induced mortality through neutrophil amplification of inflammation.

Speaks, Samuel / McFadden, Matthew I / Zani, Ashley / Solstad, Abigail / Leumi, Steve / Roettger, Jack E / Kenney, Adam D / Bone, Hannah / Zhang, Lizhi / Denz, Parker J / Eddy, Adrian C / Amer, Amal O / Robinson, Richard T / Cai, Chuanxi / Ma, Jianjie / Hemann, Emily A / Forero, Adriana / Yount, Jacob S

Nature communications

2024 Volume 15, Issue 1, Page(s) 2751

Abstract: ... forming protein gasdermin D (GSDMD) during infection. Ablation of GSDMD in knockout (KO) mice (Gsdmd ...

Abstract	Influenza virus activates cellular inflammasome pathways, which can be both beneficial and detrimental to infection outcomes. Here, we investigate the function of the inflammasome-activated, pore-forming protein gasdermin D (GSDMD) during infection. Ablation of GSDMD in knockout (KO) mice (Gsdmd
MeSH term(s)	Animals ; Mice ; Neutrophils/metabolism ; Gasdermins ; Inflammasomes/genetics ; Inflammasomes/metabolism ; Inflammation/genetics ; Inflammation/metabolism ; Orthomyxoviridae/metabolism ; Phosphate-Binding Proteins/genetics ; Phosphate-Binding Proteins/metabolism
Chemical Substances	Gasdermins ; Inflammasomes ; Phosphate-Binding Proteins
Language	English
Publishing date	2024-03-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-47067-0
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Article: Page Kidney: An Unusual Complication of a Renal Transplant Biopsy.

McFadden, Jacob D / Hawksworth, Jason S

Case reports in urology

2018 Volume 2018, Page(s) 8768549

Abstract: Page kidney, a rare phenomenon whereby external compression of renal parenchyma can induce hypertension, can be caused by subcapsular hematoma following renal transplant biopsy. Surgical intervention is often warranted to salvage the transplant kidney. ... ...

Abstract	Page kidney, a rare phenomenon whereby external compression of renal parenchyma can induce hypertension, can be caused by subcapsular hematoma following renal transplant biopsy. Surgical intervention is often warranted to salvage the transplant kidney. This is a case report of a patient with acute T-cell-mediated rejection and no other risk factors for postprocedural bleeding that developed Page kidney. The patient had no signs or symptoms for >24 hours from the time of biopsy, underscoring the need for awareness of this rare but potentially catastrophic complication of renal transplant biopsies.
Language	English
Publishing date	2018-04-24
Publishing country	United States
Document type	Case Reports
ZDB-ID	2627659-8
ISSN	2090-6978 ; 2090-696X
ISSN (online)	2090-6978
ISSN	2090-696X
DOI	10.1155/2018/8768549
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Article: Unusual Suspect: A Case Report of Tubulocystic Renal Cell Carcinoma with Features of Cystic Renal Oncocytoma.

McFadden, Jacob D / Sesterhenn, Isabell A / Kern, Sean Q

Case reports in urology

2019 Volume 2019, Page(s) 2919686

Abstract: Tubulocystic renal cell carcinoma is an uncommon subtype of renal cell carcinoma that was only recently acknowledged by the World Health Organization. There is a relatively small collection of literature dedicated to the features and clinical course of ... ...

Abstract	Tubulocystic renal cell carcinoma is an uncommon subtype of renal cell carcinoma that was only recently acknowledged by the World Health Organization. There is a relatively small collection of literature dedicated to the features and clinical course of this lesion. Despite its rarity, this diagnosis should remain in the differential for all cystic renal masses. We present a case report of tubulocystic renal cell carcinoma (TC-RCC) with remarkable similarity to cystic renal oncocytoma, highlighting the diagnostic challenges associated with this unusual renal malignancy.
Language	English
Publishing date	2019-08-05
Publishing country	United States
Document type	Case Reports
ZDB-ID	2627659-8
ISSN	2090-6978 ; 2090-696X
ISSN (online)	2090-6978
ISSN	2090-696X
DOI	10.1155/2019/2919686
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Article ; Online: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for seminoma: Limitations of surgical intervention after first-line chemotherapy.

Tachibana, Isamu / Alabd, Andre / Whaley, Rumeal D / McFadden, Jacob / Piroozi, Alex / Hassoun, Rebecca / Kern, Sean Q / King, Jennifer / Adra, Nabil / Rice, Kevin R / Foster, Richard S / Einhorn, Lawrence H / Cary, Clint / Masterson, Timothy A

Urologic oncology

2023 Volume 41, Issue 9, Page(s) 394.e1–394.e6

Abstract: Purpose: Patients with relapsed seminoma after first-line chemotherapy can be treated with salvage chemotherapy or postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). Based on prior experience, surgical management can have worse efficacy ... ...

Abstract	Purpose: Patients with relapsed seminoma after first-line chemotherapy can be treated with salvage chemotherapy or postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). Based on prior experience, surgical management can have worse efficacy and increased morbidity compared to nonseminomatous germ cell tumor. Our aim was to characterize the surgical efficacy and difficulty in highly selected patients with residual disease after first-line chemotherapy. Materials and methods: The Indiana University testis cancer database was queried to identify men who underwent PC-RPLND for seminoma between January 2011 and December 2021. Included patients underwent first-line chemotherapy and had evidence of retroperitoneal disease progression. Results: We identified 889 patients that underwent PC-RPLND, of which only 14 patients were operated on for seminoma. One patient was excluded for lack of follow-up. Out of 13 patients, only 3 patients were disease free with surgery only. Median follow up time was 29.9 months (interquartile ranges : 22.6-53.7). Two patients died of disease. The remaining 8 patients were treated successfully with salvage chemotherapy. During PC-RPLND, 4 patients required nephrectomy, 1 patient required an aortic graft, 2 patients required a partial ureterectomy, and 3 patients required partial or complete caval resection. Conclusion: The decision between salvage chemotherapy and PC-RPLND as second-line therapy can be challenging. Salvage chemotherapy is effective but is associated with short and long-term morbidity. Surgical efficacy in this setting seems to be limited, but careful selection of patients may lead to surgical success without affecting the ability to receive any systemic salvage therapies if necessary or causing life-threating morbidity.
MeSH term(s)	Male ; Humans ; Seminoma/drug therapy ; Seminoma/surgery ; Seminoma/pathology ; Treatment Outcome ; Lymph Node Excision ; Neoplasms, Germ Cell and Embryonal/surgery ; Testicular Neoplasms/drug therapy ; Testicular Neoplasms/surgery ; Testicular Neoplasms/pathology ; Retroperitoneal Space/surgery ; Retroperitoneal Space/pathology ; Retrospective Studies
Language	English
Publishing date	2023-08-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1336505-8
ISSN	1873-2496 ; 1078-1439
ISSN (online)	1873-2496
ISSN	1078-1439
DOI	10.1016/j.urolonc.2023.06.019
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Article ; Online: Engineered resveratrol-loaded fibrous scaffolds promotes functional cardiac repair and regeneration through Thioredoxin-1 mediated VEGF pathway.

Campbell, Jacob D / Lakshmanan, Rajesh / Selvaraju, Vaithinathan / Accorsi, Diego / McFadden, David W / Maulik, Nilanjana / Thirunavukkarasu, Mahesh

International journal of pharmaceutics

2021 Volume 597, Page(s) 120236

Abstract: Despite recent advancements, mortality due to coronary heart disease (CHD) remains high. Recently, the use of tissue-engineered grafts and scaffolds has emerged as a candidate for supporting the myocardium after an ischemic event. Resveratrol is a ... ...

Abstract	Despite recent advancements, mortality due to coronary heart disease (CHD) remains high. Recently, the use of tissue-engineered grafts and scaffolds has emerged as a candidate for supporting the myocardium after an ischemic event. Resveratrol is a naturally occurring plant-based non-flavonoid polyphenolic compound found in many natural foods, including grapes and red wine. We embedded resveratrol in a polycaprolactone (PCL) scaffold and evaluated the cardio-therapeutic effects in a murine model of myocardial infarction (MI), with animals being grouped into Sham (S), Myocardial Infarction (MI), MI + PCL, and MI + PCL-Resveratrol (MI + PCL-R). After 4 and 8 weeks, echocardiography was performed to assess ejection fraction (EF) and fractional shortening (FS), which was followed by immunohistochemistry and immunofluorescence analysis at 8 weeks. The MI + PCL-R group showed a significant improvement in EF and FS compared with the MI + PCL group at 4 and 8-weeks post-surgery. PCL-R scaffolds treated hearts revealed decreased inflammatory cell infiltration, improved collagen extracellular matrix (ECM) secretion and blood vessel network formation following MI. The immunofluorescence analysis revealed resveratrol-loaded scaffolds promote increased expression of cTnT, Cx-43, Trx-1, and VEGF proteins. This study reports resveratrol-mediated rescue of ischemic myocardium when delivered through a biodegradable polymeric scaffold system after MI.
MeSH term(s)	Animals ; Mice ; Myocardial Infarction/drug therapy ; Myocardium ; Regeneration ; Resveratrol ; Thioredoxins ; Vascular Endothelial Growth Factor A
Chemical Substances	Txn1 protein, mouse ; Vascular Endothelial Growth Factor A ; vascular endothelial growth factor A, mouse ; Thioredoxins (52500-60-4) ; Resveratrol (Q369O8926L)
Language	English
Publishing date	2021-02-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2021.120236
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Article ; Online: A chromosomal inversion contributes to divergence in multiple traits between deer mouse ecotypes.

Hager, Emily R / Harringmeyer, Olivia S / Wooldridge, T Brock / Theingi, Shunn / Gable, Jacob T / McFadden, Sade / Neugeboren, Beverly / Turner, Kyle M / Jensen, Jeffrey D / Hoekstra, Hopi E

Science (New York, N.Y.)

2022 Volume 377, Issue 6604, Page(s) 399–405

Abstract: How locally adapted ecotypes are established and maintained within a species is a long-standing question in evolutionary biology. Using forest and prairie ecotypes of deer mice ( ...

Abstract	How locally adapted ecotypes are established and maintained within a species is a long-standing question in evolutionary biology. Using forest and prairie ecotypes of deer mice (
MeSH term(s)	Animals ; Chromosome Inversion ; Ecotype ; Gene Flow ; Peromyscus/genetics ; Recombination, Genetic
Language	English
Publishing date	2022-07-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abg0718
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Article ; Online: Oncolytic Orf virus licenses NK cells via cDC1 to activate innate and adaptive antitumor mechanisms and extends survival in a murine model of late-stage ovarian cancer.

van Vloten, Jacob P / Matuszewska, Kathy / Minow, Mark A A / Minott, Jessica A / Santry, Lisa A / Pereira, Madison / Stegelmeier, Ashley A / McAusland, Thomas M / Klafuric, Elaine M / Karimi, Khalil / Colasanti, Joseph / McFadden, D Grant / Petrik, James J / Bridle, Byram W / Wootton, Sarah K

Journal for immunotherapy of cancer

2022 Volume 10, Issue 3

Abstract: Background: Novel therapies are needed to improve outcomes for women diagnosed with ovarian cancer. Oncolytic viruses are multifunctional immunotherapeutic biologics that preferentially infect cancer cells and stimulate inflammation with the potential ... ...

Abstract	Background: Novel therapies are needed to improve outcomes for women diagnosed with ovarian cancer. Oncolytic viruses are multifunctional immunotherapeutic biologics that preferentially infect cancer cells and stimulate inflammation with the potential to generate antitumor immunity. Herein we describe Methods: The immunotherapeutic potential of OrfV was tested in the ID8 orthotopic mouse model of end-stage epithelial ovarian carcinoma. Immune cell profiling, impact on secondary lesion development and survival were evaluated in OrfV-treated mice as well as in Batf3 knockout, mice depleted of specific immune cell subsets and in mice where the primary tumor was removed. Finally, we interrogated gene expression datasets from primary human ovarian tumors from the International Cancer Genome Consortium database to determine whether the interplay we observed between natural killer (NK) cells, classical type 1 dendritic cells (cDC1s) and T cells exists and influences outcomes in human ovarian cancer. Results: OrfV was an effective monotherapy in a murine model of advanced-stage epithelial ovarian cancer. OrfV intervention relied on NK cells, which when depleted abrogated antitumor CD8 Conclusions: The data herein support the translational potential of OrfV as an NK stimulating immunotherapeutic for the treatment of advanced-stage ovarian cancer.
MeSH term(s)	Animals ; Carcinoma, Ovarian Epithelial ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Humans ; Killer Cells, Natural ; Licensure ; Mice ; Oncolytic Virotherapy ; Oncolytic Viruses ; Orf virus/genetics ; Orf virus/metabolism ; Ovarian Neoplasms ; Sheep
Language	English
Publishing date	2022-02-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2021-004335
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Article ; Online: Race-specific prostate cancer outcomes in a cohort of military health care beneficiaries undergoing surgery: 1990-2017.

Oehrlein, Nathan / Streicher, Samantha A / Kuo, Huai-Ching / Chaurasia, Avinash / McFadden, Jacob / Nousome, Darryl / Chen, Yongmei / Stroup, Sean P / Musser, John / Brand, Timothy / Porter, Christopher / Rosner, Inger L / Chesnut, Gregory T / Onofaro, Kayla C / Rebbeck, Timothy R / D'Amico, Anthony / Lu-Yao, Grace / Cullen, Jennifer

Cancer medicine

2022 Volume 11, Issue 22, Page(s) 4354–4365

Abstract: Background: There is substantial variability in prostate cancer (PCa) mortality rates across Caucasian American (CA), African American (AA), Asian, and Hispanic men; however, these estimates are unable to disentangle race or ethnicity from confounding ... ...

Abstract	Background: There is substantial variability in prostate cancer (PCa) mortality rates across Caucasian American (CA), African American (AA), Asian, and Hispanic men; however, these estimates are unable to disentangle race or ethnicity from confounding factors. The current study explores survival differences in long-term PCa outcomes between self-reported AA and CA men, and examines clinicopathologic features across self-reported CA, AA, Asian, and Hispanic men. Methods: This retrospective cohort study utilized the Center for Prostate Disease Research (CPDR) Multi-center National Database from 1990 to 2017. Subjects were consented at military treatment facilities nationwide. AA, CA, Asian, or Hispanic men who underwent radical prostatectomy (RP) for localized PCa within the first year of diagnosis were included in the analyses. Time from RP to biochemical recurrence (BCR), BCR to metastasis, and metastasis to overall death were evaluated using Kaplan-Meier unadjusted estimation curves and adjusted Cox proportional hazards regression. Results: This study included 7067 men, of whom 5155 (73%) were CA, 1468 (21%) were AA, 237 (3%) were Asian, and 207 (3%) were Hispanic. AA men had a significantly decreased time from RP to BCR compared to CA men (HR = 1.25, 95% CI = 1.06-1.48, p = 0.01); however, no difference was observed between AA and CA men for a time from BCR to metastasis (HR = 0.73, 95% CI = 0.39-1.33, p = 0.302) and time from metastasis to overall death (HR = 0.67, 95% CI = 0.36-1.26, p = 0.213). Conclusions: In an equal access health care setting, AA men had a shorter survival time from RP to BCR, but comparable survival time from BCR to metastasis and metastasis to overall death.
MeSH term(s)	Male ; Humans ; Retrospective Studies ; Military Health ; Neoplasm Recurrence, Local/pathology ; Prostatic Neoplasms/pathology ; Prostatectomy ; Prostate-Specific Antigen ; Cohort Studies
Chemical Substances	Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2022-05-31
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.4787
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Article ; Online: Role of Pellino-1 in Inflammation and Cardioprotection following Severe Sepsis: A Novel Mechanism in a Murine Severe Sepsis Model

Thirunavukkarasu, Mahesh / Swaminathan, Santosh / Kemerley, Andrew / Pradeep, Seetur R / Lim, Sue Ting / Accorsi, Diego / Wilson, Rickesha / Campbell, Jacob / Saad, Ibnalwalid / Yee, Siu-Pok / Palesty, J Alexander / McFadden, David W / Maulik, Nilanjana

Cells

2023 Volume 12, Issue 11

Abstract: Objectives: Intra-abdominal sepsis is commonly diagnosed in the surgical population and remains the second most common cause of sepsis overall. Sepsis-related mortality remains a significant burden in the intensive care unit despite advances in critical ...

Abstract	Objectives: Intra-abdominal sepsis is commonly diagnosed in the surgical population and remains the second most common cause of sepsis overall. Sepsis-related mortality remains a significant burden in the intensive care unit despite advances in critical care. Nearly a quarter of the deaths in people with heart failure are caused by sepsis. We have observed that overexpression of mammalian Pellino-1 (Peli1), an E3 ubiquitin ligase, causes inhibition of apoptosis, oxidative stress, and preservation of cardiac function in a myocardial infarction model. Given these manifold applications, we investigated the role of Peli1 in sepsis using transgenic and knockout mouse models specific to this protein. Therefore, we aimed to explore further the myocardial dysfunction seen in sepsis through its relation to the Peli 1 protein by using the loss of function and gain-of-function strategy. Methods: A series of genetic animals were created to understand the role of Peli1 in sepsis and the preservation of heart function. Wild-type, global Peli1 knock out (Peli1 Results: AMPEL1 Conclusion: Our results indicate that overexpression of Peli1 is a novel approach that not only preserved cardiac function but reduced inflammatory markers and apoptosis following severe sepsis in a murine genetic model.
MeSH term(s)	Mice ; Animals ; Tumor Necrosis Factor-alpha ; Interleukin-6 ; Myocytes, Cardiac ; Inflammation/complications ; Sepsis/complications ; Mammals ; Nuclear Proteins/genetics ; Ubiquitin-Protein Ligases/genetics
Chemical Substances	Tumor Necrosis Factor-alpha ; Interleukin-6 ; Peli1 protein, mouse (EC 6.3.2.-) ; Nuclear Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2023-06-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12111527
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Article: Barriers to accessing urethroplasty.

Consolo, Michael J / Syed, Kirin K / Robison, Christopher / McFadden, Jacob / Shalowitz, David I / Brown, Gordon A / Sussman, David O / Figler, Bradley D

Reviews in urology

2017 Volume 18, Issue 4, Page(s) 188–193

Abstract: Urethroplasty is an effective treatment for men with anterior urethral strictures, but is utilized less frequently than ineffective treatments such as internal urethrotomy. We sought to identify provider-level barriers to urethroplasty. An anonymous ... ...

Abstract	Urethroplasty is an effective treatment for men with anterior urethral strictures, but is utilized less frequently than ineffective treatments such as internal urethrotomy. We sought to identify provider-level barriers to urethroplasty. An anonymous online survey was emailed to all Mid-Atlantic American Urological Association members. Six scenarios in which urethroplasty was the most appropriate treatment were presented. Primary outcome was recommendation for urethroplasty in ≥ three clinical scenarios. Other factors measured include practice zip code, urethroplasty training, and proximity to a urethroplasty surgeon. Multivariate logistic regression identified factors associated with increased likelihood of urethroplasty recommendation. Of 670 members emailed, 109 (16%) completed the survey. Final analysis included 88 respondents. Mean years in practice was 17.2. Most respondents received formal training in urethroplasty: 43 (49%) in residency, 5 (6%) in fellowship, and 10 (11%) in both; 48 respondents (55%) had a urethroplasty surgeon in their practice, whereas 18 (20%) had a urethroplasty surgeon within 45 minutes of his or her primary practice location. The only covariate that was associated with an increased likelihood of recommending urethroplasty in ≥ three scenarios was formal urethroplasty training. Most members (68%) reported no barriers to referring patients for urethroplasty; the most common barriers cited were long distance to urethroplasty surgeon (n 5 13, 15%) and concern about complications (n 5 8, 9%). Urethroplasty continues to be underutilized in men with anterior urethral strictures, potentially due to lack of knowledge dissemination and access to a urethroplasty surgeon. Appropriate urethroplasty utilization may increase with greater exposure to urethroplasty in training.
Language	English
Publishing date	2017-01-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2108895-0
ISSN	2153-8182 ; 1523-6161
ISSN (online)	2153-8182
ISSN	1523-6161
DOI	10.3909/riu0731
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